Renin-Angiotensin-Aldosterone System Blockade (RAASB) After Acute Kidney Injury: The Controversy Thickens on If and When to Discontinue RAASB.

Unquestionably, there is a common consensus regarding cardiorenal protection with renin-angiotensin-aldosterone system blockade (RAASB) in both diabetic and nondiabetic chronic kidney disease (CKD). Nevertheless, there remain conflicting retrospective reports regarding renal and cardiovascular mortality outcomes following discontinuation of RAASB in advanced CKD. We present an editorial on a recent article discussing renal and mortality outcomes among hospitalized veterans who were started back on RAASB versus those who were not started back on RAASB. The controversy surrounding this topic thickens as the analysis unfolds.

A Four-Year Report on Renal Outcomes Following the Elective Withdrawal of Long-Term Renin-Angiotensin-Aldosterone Blockade in a Cohort of Patients With Otherwise Inexplicable New-Onset and Progressive Acute Kidney Injury.

Background Renin-angiotensin-aldosterone (RAAS) blockade is acclaimed, by consensus, to be renoprotective in both diabetic and non-diabetic chronic kidney disease (CKD). Contradictory reports exist regarding renal and cardiovascular outcomes after stopping RAAS blockade in advanced CKD. A few prospective, non-randomized, cohort studies have demonstrated improvement in kidney function after discontinuation of RAAS blockade. In this study, we investigated renal and mortality outcomes following the elective withdrawal of RAAS blockade after otherwise inexplicable acute kidney injury (AKI). Methodology We conducted a retrospective cohort analysis of patients enrolled between February 2018 and May 2021. Kidney function was monitored after elective withdrawal of long-term RAAS blockade in CKD patients presenting with new-onset otherwise inexplicable progressive AKI, defined by a >25% increase in baseline serum creatinine. Results In total, 71 patients, 69 Caucasians, one African American, and one Hispanic, were included in the study, with a male-to-female ratio of 42:29, and a mean age of 69.4 (37-95) years. Through February 2022, 12 patients had died, with eight remaining on hemodialysis for end-stage renal disease. Of the remaining 51 patients followed for 706 (40-1,478) days, baseline serum creatinine was 1.30 ± 0.42 (0.66-2.70) mg/dL, peak enrollment serum creatinine was 2.17 ± 1.06 (1.1-8.3) mg/dL (n = 51, p < 0.0001, t = 6.4872, df = 135), and serum creatinine after four years was 1.58 ± 0.54 (0.84-3.3) mg/dL (n = 50, p < 0.0001, t = 5.1805, df = 119). Death in 11 of 12 (91%) patients was from non-renal causes, and most deaths occurred despite improved kidney function. Conclusions Our results demonstrate clearly improved renal outcomes in most patients following the elective withdrawal of long-term RAAS blockade in CKD patients with new-onset progressive yet otherwise inexplicable AKI without increased cardiovascular mortality.

Pseudohyperkalemia and the Need for Imperative Caution With the Newly Introduced Potent Potassium Binders: Two Cases.

Pseudohyperkalemia was first reported in 1955 by Hartmann and Mellinkoff, as a marked elevation of serum potassium in the absence of clinical evidence of electrolyte imbalance - simultaneous serum potassium exceeds plasma potassium by >0.4 mmol/L. We describe two patients with pseudohyperkalemia who inadvertently received inappropriate potassium binder therapy for weeks to months before the diagnosis of pseudohyperkalemia was entertained and subsequently confirmed. Potassium binders ultimately were promptly discontinued once the diagnosis of pseudohyperkalemia was confirmed. Physicians' attention must be drawn to the availability of the new potent oral potassium binders, patiromer and sodium zirconium cyclosilicate. We strongly advocate for imperative caution with these new binders. Iatrogenic life-threatening hypokalemia remains a real concern and must be avoided. Our patients highlighted the importance of caution in the use of the newer potent potassium binders to mitigate against the causation of iatrogenic hypokalemia. Also as important is the observation that in the same patient, with changing clinical scenarios, a patient might exhibit true hyperkalemia that alternated with pseudohyperkalemia, the first of such a report.

Page Kidney Complicating Kidney Biopsy after Stopping Apixaban: A Physician's Dilemma.

Page kidney was described by Page, following very elaborate experiments with animal kidneys in 1939, with persistent arterial hypertension from "cellophane perinephritis." Subsequently, it was reported after trauma, from renal cysts and tumors, and from intrarenal hematoma complicating percutaneous kidney biopsy. We describe Page kidney associated with acute kidney injury 26 days after an uncomplicated ultrasound-guided right native kidney biopsy. Patient was on Apixaban, a non-vitamin K antagonist oral anticoagulant (NOAC) for atrial fibrillation which was withheld 3 days before the procedure. It was restarted 3 days after. The evidence-base supporting guidelines and recommendations for the peri-procedural management of the NOACs is inadequate, sparse, and often conflicted. More research is warranted.

Post-Renal Biopsy Acute Kidney Injury and Page Kidney from Intra-Renal Hematoma Aggravated by Reversible Contrast-Induced Nephropathy Following Renal Arterial Embolization.

BACKGROUND Page kidney was described by Dr. Irving Page in animal kidneys in 1939 with renal failure and persistent arterial hypertension from "cellophane perinephritis". By 2009, about 100 cases of Page kidney had been reported. Bleeding complications after percutaneous kidney biopsy has, however, been well described. Moreover, the perioperative management of the recently introduced non-vitamin K antagonist anticoagulants (NOACs) remains uncertain due to inadequate evidence. Current guidelines to determine the appropriate duration of withholding NOACs before a surgical procedure, and when to restart NOACs safely after a procedure, however, cognizant of the implications of renal dysfunction, and levels of risk of the procedure are still unclear and sometimes conflicted. CASE REPORT We describe a case of Page kidney from an intrarenal hematoma complicating ultrasound-guided percutaneous right native kidney biopsy with acute kidney injury after withholding apixaban, a NOAC, for 3 days. Computed tomography evidence of continuing intrarenal bleeding from a renal pseudoaneurysm was treated with super-selective renal artery embolization; the case was further complicated by superimposed acute kidney injury from contrast-induced nephropathy. CONCLUSIONS We reviewed the vagaries of Page kidney with respect to the presence, or otherwise, of hypertension and how to explain worsening renal failure despite only unilateral involvement of a single kidney in a patient with 2 kidneys. Furthermore, we revisit the risks of contrast-induced nephropathy following iodinated contrast exposure. We explored the alternative management options for a post-biopsy renal pseudoaneurysm, that would avoid the use of iodinated contrast that could have potentially mitigated, if not fully prevented, the ensuing contrast-induced acute kidney injury.

Hospital Readmission among New Dialysis Patients Associated with Young Age and Poor Functional Status.

BACKGROUND/AIMS: Over one-third of hospital discharges among dialysis patients are followed by 30-day readmission. The first year after dialysis start is a high-risk time frame. We examined the rate, causes, timing, and predictors of 30-day readmissions among adult, incident dialysis patients. METHODS: Hospital readmissions were assessed from the 91st day to the 15th month after the initiation of dialysis using a Mayo Clinic registry linkage to United States Renal Data System claims during the period January 2001-December 2010. RESULTS: Among 1,727 patients with ≥1 hospitalization, 532 (31%) had ≥1, and 261 (15%) had ≥2 readmissions. Readmission rate was 1.1% per person-day post-discharge, and the highest rates (2.5% per person-day) occurred ≤5 days after index admission. The overall cumulative readmission rate was 33.8% at day 30. Common readmission diagnoses included cardiac issues (22%), vascular disorders (19%), and infection (13%). Similar-cause readmissions to index hospitalization were more common during days 0-14 post-discharge than days 15-30 (37.5 vs. 22.9%; p = 0.004). Younger age at dialysis initiation, inability to transfer/ambulate, serum creatinine ≤5.3 mg/dL, higher number of previous hospitalizations, and longer duration on dialysis were associated with higher readmission rates in multivariable analyses. Patients aged 18-39 were few (8.3%) but comprised 17.7% of "high-readmission" users such that a 30-year-old patient had an 87% chance of being readmitted within 30 days of any hospital discharge, whereas an 80-year-old patient had a 25% chance. CONCLUSIONS: Overall, 30-day readmissions are common within the first year of dialysis start. The first 10-day period after discharge, young patients, and those with poor functional status represent key areas for targeted interventions to reduce readmissions.

Unexplained hypotension and exertional dyspnea in a night-cycled peritoneal dialysis patient--a rare form of icodextrin hypersensitivity.

In recent years, icodextrin 7.5% has been used in PD as an alternative to glucose to achieve sustained reliable ultrafiltration (UF) and clearance without adversely increasing glucose absorption. Icodextrin is generally well tolerated. The most commonly reported adverse events are cutaneous reactions. We report a rare form of hypersensitivity to icodextrin 7.5% that was accompanied by dyspnea and symptomatic hypotension, without increased UF to account for the observed hypotension. Icodextrin produces symptomatic hypotension in up to 40% of patients by a known mechanism of increased UF and corresponding weight loss. However, it can also produce symptomatic hypotension accompanied by several other systemic symptoms in a hypersensitivity reaction. Discontinuation of the icodextrin results in prompt resolution of those symptoms. Treating nephrologists must be aware of this rare form of icodextrin hypersensitivity.

Nondialytic therapy for end-stage renal disease is an underutilized care paradigm in the United States: time for a more robust reappraisal of this treatment option.

Nondialytic therapy (NDT)--also calledconservative kidney management--is a growing modality of treatment for select chronic kidney disease and end-stage renal disease (ESRD) patients globally. Nevertheless, NDT is rarely practiced in the United States. We set out to investigate NDT activity before initiation of renal replacement therapy in a Northwestern Wisconsin Mayo Clinic ESRD population. Records of all prevalent ESRD patients on chronic hemodialysis in our practice were retrospectively reviewed in May 2012. Dialysis nurses and social workers were informally interviewed to augment the review process. Of the 166 ESRD patients reviewed, 82 (49%) were 70 years of age or older, 46 (28%) were 70-79 years, and 36 (22%) were 80-89 years. Most of these older patients had multiple significant comorbidities ("multimorbidity"). Evidence for NDT activity before initiation of renal replacement therapy was virtually nonexistent. The older ESRD patients with multimorbidity experienced frequent hospitalizations. Our preliminary review suggests that their quality of life may have been better with NDT. Almost one half of our ESRD population was made up of people more than 70 years of age, most with multimorbidity. In our practice, NDT is a neglected paradigm, as it is in most U.S. nephrology practices. The place of NDT, actively provided by a specialized multidisciplinary team, for U.S. ESRD patients demands urgent attention and robust reappraisal by U.S. nephrologists.

Evidence of the syndrome of rapid onset end-stage renal disease (SORO-ESRD) in the acute kidney injury (AKI) literature--preventable causes of AKI and SORO-ESRD--a call for re-engineering of nephrology practice paradigms.

INTRODUCTION: We described the previously unrecognized syndrome of rapid-onset end-stage renal disease (SORO-ESRD) in 2010, in the journal Renal Failure, as distinct from the classic CKD-ESRD progression of a methodical, linear, time-dependent and predictable progression from CKD through CKD stages I-V, ending in ESRD requiring renal replacement therapy (RRT). It remains unclear to what extent this syndrome may have been identified in the past without acknowledging its uniqueness. METHODS: We reviewed AKI reports and ascertained cases of SORO-ESRD as defined by patients with a priori stable kidney function who subsequently exhibited unanticipated and irreversible ESRD requiring RRT following new AKI episodes. RESULTS: Fifteen AKI reports demonstrating SORO-ESRD were analyzed. The reports span most regions of the world. The 15 studies with 20 to 1095 AKI patients each, mean age 39-65 years, published between 1975 and 2010, demonstrated SORO-ESRD rates from 1% to 85% of the AKI series. AKI was caused by hypovolemia/hypotension, infections/sepsis and exposure to nephrotoxics especially radiocontrast, NSAIDs, aminoglycosides and RAAS blocking agents, ACEIs and ARBs. DISCUSSION: Irreversible ESRD following AKI, consistent with our recent description of a new and unrecognized syndrome has been sporadically reported in the AKI literature, without a clear mandate as a syndrome, potentially distinct from the classic ESRD. The contribution of SORO-ESRD to the global ESRD pandemic, the impact of SORO-ESRD on AV-Fistula planning, any differential behavior of SORO-ESRD versus classic ESRD in terms of mortality outcomes and any predisposing factors to SORO-ESRD as advanced age and nephrotoxic exposure all call for serious research study.

The CKD enigma with misleading statistics and myths about CKD, and conflicting ESRD and death rates in the literature: results of a 2008 U.S. population-based cross-sectional CKD outcomes analysis.

The just released (August 2012) U.S. Preventive Services Task Force (USPSTF) report on chronic kidney disease (CKD) screening concluded that we know surprisingly little about whether screening adults with no signs or symptoms of CKD will improve health outcomes and that clinicians and patients deserve better information on CKD. The implications of the recently introduced CKD staging paradigm versus long-term renal outcomes remain uncertain. Furthermore, the natural history of CKD remains unclear. We completed a comparison of US population-wide CKD to projected annual incidence of end stage renal disease (ESRD) for 2008 based on current evidence in the literature . Projections for new ESRD resulted in an estimated 840,000 new ESRD cases in 2008, whereas the actual reported new ESRD incidence in 2008, according to the 2010 USRDS Annual Data Report, was in fact only 112,476, a gross overestimation by about 650%. We conclude that we as nephrologists in particular, and physicians in general, still do not understand the true natural history of CKD. We further discussed the limitations of current National Kidney Foundation Disease Outcomes Quality Initiative (NKF KDOQI) CKD staging paradigms. Moreover, we have raised questions regarding the CKD patients who need to be seen by nephrologists, and have further highlighted the limitations and intricacies of the individual patient prognostication among CKD populations when followed overtime, and the implications of these in relation to future planning of CKD care in general. Finally, the clear heterogeneity of the so-called CKD patient is brought into prominence as we review the very misleading concept of classifying and prognosticating all CKD patients as one homogenous patient population.

Renoprevention: A new concept for reengineering nephrology care--an economic impact and patient outcome analysis of two hypothetical patient management paradigms in the CCU.

BACKGROUND: The impact of acute kidney injury (AKI) on chronic kidney disease (CKD) progression remains uncertain; the common belief is that AKI in CKD is short-lived with subsequent full recovery. However 25.2% of end-stage renal disease (ESRD) Medicare patients all experienced antecedent AKI. We recently described a new syndrome of ESRD following AKI, the syndrome of rapid-onset end-stage renal disease (SORO-ESRD). Renoprevention, which we described in 2009, is the application of preventative measures to reduce AKI incidence. METHODS: This is a descriptive study based on real clinical experience. Two hypothetical 69-year-old Caucasian male patients, A and B, with symptomatic coronary artery disease (CAD) presented for elective cardiac catheterization and subsequent coronary artery bypass graft procedures; renoprevention was applied in patient A but not in B. RESULTS: Aggressive fluid repletion, withholding Lisinopril 40 mg once daily (QD) 1 week before hospitalization (hydralazine substituted) in A-earlier discharge after 6 days, transient minimal change in serum creatinine. Patient B continued on Lisinopril 40 mg QD, experienced prolonged hypotension needing pressors-severe oliguric AKI, volume overload, daily RRT for 6 days, recovered kidney function, was discharged after 20 days. Hospital charges were $68,580 (A) versus $154,650 (B). If patient B had developed ESRD (SORO-ESRD), the savings would be humongous. CONCLUSION: A more forceful and pragmatic application of renoprevention strategies in the coronary care unit (CCU)-preemptive withholding of nephrotoxics including renin angiotensin aldosterone system (RAAS) blockers, aggressive prevention of perioperative hypotension, avoiding nephrotoxic exposure as contrast, and antibiotics-leads to less AKI, potentially less SORO-ESRD, better patient outcomes, and massive dollar savings. Such paradigm shifts would constitute major rethinking in current nephrology practice, a form of nephrology practice reengineering.

De novo HBV infection in a Mayo Clinic hemodialysis population: economic impact of reduced HBV testing and a call for changes in current US CDC guidelines on HBV testing protocols.

Hemodialysis (HD) exposes end-stage renal disease patients to significantly higher risks for Hepatitis B Virus (HBV) infection, a major public health scourge. Therefore, current US CDC guidelines, last revised in 2001, call for monthly HbsAg tests. The charge to Medicare per HbsAg test is $100. In an economic analysis, we hypothesized that in the new environment of Medicare Fee Bundling, this is unwise and wasteful if de novo HBV infection rate among HD patients is <1%. We determined de novo HBV infection rate among a Mayo Clinic HD cohort, July 2000-July 2010. A retrospective analysis of all relevant medical records of the cohort was completed to identify de novo HBV infection. Nine hundred sixty-five HD patients were analyzed. One case of de novo HBV infection was identified in a 54-year old known IV drug user, a previous Hepatitis C carrier. This translates to a de novo HBV case incidence rate of 0.1%. De novo HBV infection among HD patients in the US, 2000-2010, is only 0.1%. In the early 1970s, rates were as high as 30%. We recommend 3-monthly HbsAg testing, but to continue current monthly testing for IV drug users and other high-risk groups. Huge cost savings would result, without any compromise of quality outcomes. With over 500,000 HD patients, this represents a mind-boggling $40 billion savings in Medicare charges over 10 years. The US CDC should revise these outdated guidelines, last revised in 2001, to fall in line with current clinical realities on the ground.

The effects of substituting glassware for plasticware and the use of an ethanol vector on oocyte maturation in vitro.

The intent of this study was to evaluate specific technical aspects of in vitro oocyte maturation (IVM), which included container material and solvent delivery vector. Oocytes were matured in oil-free, open-well systems contained in either plastic or glass dishes and compared to control oocytes matured in media droplets on plastic dishes overlaid with mineral oil. Open-well experiments were repeated with ethanol in a quantity sufficient for delivery of nonmiscible compounds. Cleavage rates were significantly decreased in the glassware system when compared to controls. The plasticware open-well system did not differ from either the controls or the glassware groups. Cleavage in glassware with ethanol was significantly lower than controls or plasticware with ethanol. Blastocyst rates were only decreased in the glassware-ethanol treatment when compared to plasticware-ethanol treatment. Cell counts and percentage of TUNEL-positive cells did not differ significantly. Unexpectedly, sex ratio was significantly decreased (34% male) from the expected value of 50% male in the glassware group with added ethanol. The current study demonstrates the sensitivity of IVM to subtle technical changes, resulting in significant developmental consequences.

A novel approach to sexing bovine blastocysts using male-specific gene expression.

When examining gene expression profiles for the purposes of assessing embryo quality, it is imperative that sex be considered, because many embryonic transcripts have sex-related expression patterns. The objective of this study was to systematically examine eight Y chromosome linked genes (DDX3Y, EIF1AY, HSFY, SRY, TSPY, USP9Y, ZFY, and ZRSR2Y) to characterize their expression in bovine blastocysts and to examine the usefulness of this expression for the purpose of RNA-based embryo sexing. In order to examine the expression of these genes, pools of blastocysts (groups of 10 and 20) as well as single embryos (N = 50) were analyzed with reverse transcriptase polymerase chain reaction (RT-PCR) and reverse transcriptase quantitative PCR (RT-qPCR). Of the 50 single embryos, 32 were concurrently sexed with DNA-based methods. Transcripts of DDX3Y, EIF1AY, TSPY, USP9Y, ZFY and ZRSR2Y were detected in the pooled and single blastocysts, but no transcripts were detected for HSFY or SRY. After performing DNA-based sexing experiments, we concluded that this expression was restricted to the male embryos. The consistency of the expression varied according to the gene as well as the specific primer set. Three genes were expressed in the full set of male embryos, DDX3Y, USP9Y, and ZRSR2Y and therefore represent good candidates for RNA-based sexing methods.